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| General |
| Study Status |
Ongoing |
Application Number /
Requirement Number |
P170043 / PAS002 |
| Date Original Protocol Accepted |
04/16/2019
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| Date Current Protocol Accepted |
03/03/2021
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| Study Name |
New Enrollment PAS
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| Device Name |
iStent inject Trabecular Micro-Bypass System (Model G2-M-IS)
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| Clinical Trial Number(s) |
NCT01461291
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Adult: At least 22 yrs
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| Detailed Study Protocol Parameters |
| Study Objectives |
The objective of this post approval study (PAS) is to evaluate the rate of clinically relevant complications associated with iStent inject
placement and stability, as determined at 36 months in the postmarket setting compared to the pre-specified performance
target of 2%. This is a prospective, non-randomized, multicenter, single-arm, post approval study of the iStent inject with follow-up
through 3 years postoperative.
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| Study Population |
358 eyes at a minimum of 15 and up to 30 investigational sites in the U.S. It is expected that the enrollment phase will last up to 37.5
months.
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| Sample Size |
A sample size of 250 eyes can provide a statistical power of 80% at a true p of 0.05. Considering a drop-out rate of 30% at 36 months for
this post-approval study, the study should treat at least 358 eyes of 358 subjects.
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| Key Study Endpoints |
The rate of clinically relevant complications associated with iStent inject placement and stability as determined at 36 months.
Specific device-related complications include clinical sequelae resulting from device position including, but not limited to:
Secondary surgical intervention (SSI) to modify device position (e.g., repositioning or explantation)
Corneal endothelial touch by device
Corneal edema leading to BSCVA loss > 2 lines at the Month 36 visit, in comparison with preoperative BSCVA
Other Safety Outcomes:
Rate of occurrence of sight-threatening adverse events including:
Persistent (at time of study exit) BSCVA loss greater than or equal to 3 lines compared to best recorded BSCVA at any postoperative visit
Endophthalmitis
Corneal decompensation
Retinal detachment
Severe choroidal hemorrhage or detachment or aqueous misdirection
Rate of ocular secondary surgical interventions (SSI)
Rate of other adverse events including:
Increase from baseline IOP of greater than or equal to 10 mmHg at any time greater than or equal to 30 days postoperative
BSCVA loss greater than or equal to 2 lines at Month 36 compared to preoperative
BSCVA loss greater than or equal to 2 lines at Month 36 compared to best recorded
BSCVA at any postoperative visit
Device movement, defined as a stent not visible in the original location, that does not result in clinically relevant complications
as described above (e.g., SSI to modify device position, corneal endothelial touch by device, or corneal edema leading to BSCVA loss > 2 lines at the Month 36 visit compared to preoperative BSCVA), and that is not attributable to any one or more of the following:
variations in gonioscopy, OCT or UBM (or other standard imaging methods) viewing angle or illumination
changes in angle anatomy due to concomitant findings such as resolution of hyphema
changes in anterior chamber depth
development of focal peripheral anterior synechiae (PAS)
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| Follow-up Visits and Length of Follow-up |
36 months (3 years)
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| Interim or Final Data Summary |
| Interim Results |
Of the 387 subjects enrolled, 19 subjects were a screen failure, and 367 subjects underwent implantation with the study device at the time of data cutoff. Enrollment accrual is complete, and the last subject was treated on June 23, 2022.
A total of 172 postoperative study eye AEs were reported in 107/367 (29.2%) subjects. The most common AE was dry eye (18 events reported in 18 subjects; 4.9%). There were no reports of intraoperative ocular AEs or UADEs.
97.4% (342/351) at Month 12, 97.6% (326/334) at Month 24, 98.2% (270/275) at Month 36 had Best Spectacle Corrected Visual Acuity (BCVA) of 20/40 or better, and 86.0% (302/351) at Month 12, 86.5% (289/334) at Month 24, 85.8% (236/275) at Month 36 were 20/25 or better. 65/367 (17.7%) subjects had BSCVA worse than 20/40 preoperatively. 11 subjects had visual acuity worse than 20/40 at their last available visit prior to data cutoff, which includes 7 subjects with preoperative BSCVA worse than 20/40.
Additionally, mild corneal edema was observed in 5 eyes at Month 1. There were no reports of moderate or severe corneal edema after the Day 1 visit. Observations involving 2+, 3+, and 4+ anterior chamber (AC) cells were limited to postoperative Day 1 and Week 1. 1+ AC cells were reported in 2 eyes at Month 1, 1 eye at Month 3, and 1 eye at Month 6; these 4 subjects had reports of inflammation.
Postoperative goniosynechiae were reported in 8/367 subjects (6 by the same PI). 4/367 subjects had transient postoperative angle abnormalities. Visual Field Mean Deviation (MD) measurements showed a worsening of = 2.5 dB was reported in 6.9% of eyes (24/350) at Month 12 visit, in 9.7% of eyes (32/329) at Month 24, and in 14.1% of eyes (38/270) at Month 36.
Lastly, a total of 238 protocol deviations were reported for 148/367 subjects. The total rate of protocol deviations was 0.064%.
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| Actual Number of Patients Enrolled |
367
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| Actual Number of Sites Enrolled |
14
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| Patient Follow-up Rate |
Accountability at 36 months was 91.6% (318/347). Sixty-four (64) participants were implanted with Model G2-M-IS. Accountability at 36 months for the Model G2-M-IS was 91.8% (n/N). For Model G2-W, 303 participants were treated and accountability at 36 months was 91.6% (n/N).
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| Final Safety Findings |
The safety endpoint was the rate of clinically relevant complications associated with the iStent inject/iStent inject W placement and stability as determined at 36 months. Specific device-related complications included clinical sequelae resulting from device position including, but not limited to SSIs to modify device position (e.g., repositioning or explantation), corneal endothelial touch by the device, corneal edema leading to best spectacle corrected visual acuity (BSCVA) loss > 2 lines at the Month 36 visit, incomparison with preoperative BSCVA. None were reported; therefore, the rate of clinically relevant complications was (n =0%) at Month 36.
A total of 61 sight-threatening adverse events (SAEs) was reported in 39 participants (10.6%; 39/367). Rates were similar for both models. SAEs were reported in 10.9% (33/303) of participants that received Model G2-W, and 9.4% (6/64) of participants that received Model G2-M-IS. Reported SAEs included age-related macular degeneration (AMD) or worsening of AMD at a rate of 1.9% (7/367), and best spectacle corrected visual acuity (BSCVA) loss of 3 lines or more at study exit and worse than 20/40 (LogMAR 0.3) at a rate of 1.1% (4/367).
There was a total of 28 Secondary Surgical Interventions (SSIs) reported for 14 participants at a rate of 3.8% (14/367). Glaucoma-related SSIs of selective laser trabeculoplasty (SLT) was 1.9% (7/367). For Model G2-W, SLT as SSI was reported in 2.3% (7/303) of participants; no SLT as SSI was reported for Model G2-M-IS participants. Non glaucoma-related SSIs were performed for (recurrent) retinal detachment, retinal flap tear, vitreous hemorrhage, macular hole and worsening vitreous floaters in 2.2% (8/367) participants.
A total of 168 postoperative ocular adverse events (AEs) were reported for 112 participants (30.5%, 112/367). There were 10 events for 7 participants (1.9%, 7/367) of increased intraocular pressure (IOP) = 10 mmHg at any time = 30 days postoperative. There was one event that was ongoing at study exit. A total of 11 events of BSCVA loss were reported for 10 participants at a rate of 2.7% (10/367) including: 1.1% (4/367) BSCVA loss 3 lines or more at study exit vs. baseline or best recorded BSCVA at any postoperative visit and worse than 20/40; 0.5% (2/367) BSCVA loss (transient) 2 lines or more at or after 3 months postoperative; 0.8% (3/367) for BSCVA loss 2 lines or more and less than 3 lines at study exit vs. best recorded BSCVA at any postoperative visit; and 0.3% (1/367) for BSCVA loss 3 lines or more at study exit vs. baseline or best recorded BSCVA at any postoperative visit and 20/40 or better. There was one (1) case (0.3%, 1/168) of stent obsruction by iris at week one. There were two (2) participants (0.5%, 2/367) reported with Clinically Significant Cystoid Macular Edema. There was one (0.3%, 1/367) case of suspected endophthalmitis reported.
For changes in visual acuity from baseline, 1.5% (4/303) of Model G2-W participants and 1.8% (1/64) of Model G2-M-IS participant lost > 2 lines at the 36-month visit.
Of the 367 participants enrolled, 364 participants were implanted with 2 stents, 2 participants were implanted with 3 stents and 1 participant was implanted with 1 stent. All implanted stents were visible from Month 1 through all later study visits.
A total of 315 protocol deviations were reported for 175 participants. The total rate of protocol deviations (PDs) was 0.084% (315 of 375,546 potential deviations). The most common PDs were missed protocol required assessments (n=110) which included 74 PDs involving specular microscopy. There were 95 PDs of out of window visits and 57 PDs of assessment not performed per protocol.
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| Study Strengths & Weaknesses |
Strengths: The information from this new enrollment post-approval study (PAS) provides long term safety data for Model G2-W.
Weakness: There was a total of 49 participants (13%; 49/367) reported discontinued (n=20) or lost to follow-up (n=29).
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| Recommendations for Labeling Changes |
Yes
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